Cvb3-mediated mitophagy plays an important role in viral replication via abrogation of interferon pathways

Soo Jin Oh, Byung Kwan Lim, Jeanho Yun, Ok Sarah Shin

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Coxsackievirus B3 (CVB3) is a common enterovirus that causes systemic inflammatory diseases, such as myocarditis, meningitis, and encephalitis. CVB3 has been demonstrated to subvert host cellular responses via autophagy to support viral replication in neural stem cells. Mitophagy, a specialized form of autophagy, contributes to mitochondrial quality control via degrading damaged mitochondria. Here, we show that CVB3 infection induces mitophagy in human neural progenitor cells, HeLa and H9C2 cardiomyocytes. In particular, CVB3 infection triggers mitochondrial fragmentation, loss of mitochondrial membrane potential, and Parkin/LC3 translocation to the mitochondria. Rapamycin or carbonyl cyanide m-chlorophenyl hydrazone (CCCP) treatment led to increased CVB3 RNA copy number in a dose-dependent manner, suggesting enhanced viral replication via autophagy/mitophagy activation, whereas knockdown of PTEN-induced putative kinase protein 1(PINK1) led to impaired mitophagy and subsequent reduction in viral replication. Furthermore, CCCP treatment inhibits the interaction between mitochondrial antiviral signaling protein (MAVS) and TANK-binding kinase 1 (TBK1), thus contributing to the abrogation of type I and III interferon (IFN) production, suggesting that mitophagy is essential for the inhibition of interferon signaling. Our findings suggest that CVB3-mediated mitophagy suppresses IFN pathways by promoting fragmentation and subsequent sequestration of mitochondria by autophagosomes.

Original languageEnglish
Article number704494
JournalFrontiers in Cellular and Infection Microbiology
Volume11
DOIs
Publication statusPublished - 2021
Externally publishedYes

Bibliographical note

Funding Information:
This research was funded by the Basic Science Research Program of the National Research Foun-dation of Korea (NRF) by the Ministry of Science, ICT & Future Planning (NRF-2019R1A2C1005961) (to OS) and the Korea government (MSIT) (No. 2016R1A5A2007009) (to JY).

Funding Information:
This research was funded by the Basic Science Research Program of the National Research Foun-dation of Korea (NRF) by the Ministry of Science, ICT & Future Planning (NRF-2019R1A2C1005961) (to OS) and the Korea government (MSIT) (No. 2016R1A5A2007009) (to JY). ACKNOWLEDGMENTS We would like to thank Dr. Woong Sun (Korea University School of Medicine, Korea), Dr. Hye Jin Yoo (Korea University School of Medicine, Korea), and Dr. Jewook Yu (Yonsei University School of Medicine, Korea) for providing the reagents.

Publisher Copyright:
© 2021 Oh, Lim, Yun and Shin.

Keywords

  • Coxsackievirus B3 virus
  • Interferon
  • Mitochondrial dynamics
  • Mitophagy
  • Neural progenitor cells and stem cells

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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